Submissions for variant NM_004744.5(LRAT):c.470T>C (p.Leu157Pro)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004689544	SCV005185825	likely pathogenic	Leber congenital amaurosis	2024-05-15	criteria provided, single submitter	clinical testing	Variant summary: LRAT c.470T>C (p.Leu157Pro) results in a non-conservative amino acid change located in the LRAT domain (IPR007053) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-05 in 250930 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in LRAT causing Leber Congenital Amaurosis (4e-05 vs 0.0005), allowing no conclusion about variant significance. c.470T>C has been reported in the literature as homozygous in two individuals affected with retinitis pigmentosa (example: Areblom_2023). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 37510321). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic.